Salts and processes of preparing a PI3K inhibitor

Abstract

The present application provides processes for preparing (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one, which is useful as an inhibitor phosphoinositide 3-kinase-delta (PI3Kδ), as well as a salt form and intermediates related thereto.

What is claimed is: 
     
       1. A salt which is (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one hydrochloric acid salt, that is crystalline, having at least four XRPD peaks, in terms of 2-theta, selected from about 11.3°, about 16.4°, about 21.0°, about 23.0°, about 28.1°, about 31.2°, and about 32.8°. 
     
     
       2. The salt of  claim 1  that is a 1:1 stoichiometric ratio of (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one to hydrochloric acid. 
     
     
       3. The salt of  claim 1  characterized by a DSC thermogram having an endothermic peak at about 207° C. 
     
     
       4. The salt of  claim 1  having a DSC thermogram substantially as shown in  FIG. 1 . 
     
     
       5. The salt of  claim 1  having a TGA thermogram substantially as shown in  FIG. 2 . 
     
     
       6. The salt of  claim 1  having at least five XRPD peaks, in terms of 2-theta, selected from about 11.3°, about 16.4°, about 21.0°, about 23.0°, about 28.1°, about 31.2°, and about 32.8°. 
     
     
       7. The salt of  claim 1  having an XRPD profile substantially as shown in  FIG. 3 . 
     
     
       8. A pharmaceutical composition comprising a salt of  claim 1  and a pharmaceutically acceptable carrier.